Search Results (1,462)

A 6-year-old castrated male Bengal cat developed a subcutaneous mass at a previous vaccination site, which was initially diagnosed as cutaneous T-cell lymphoma following surgical excision at a local hospital. The cat was referred for metastatic evaluation and further treatment. Computed tomography revealed a residual tumor at the excision site, and an additional thoracic subcutaneous mass was identified. Both lesions were surgically excised and submitted for histopathologic and immunohistochemical examination. Despite the initial diagnosis of lymphoma, immunohistochemistry demonstrated that the neoplastic cells were negative for multiple lineage-specific markers, including CD3, Pax5, CD20, and cytokeratin, but showed strong MUM-1 positivity in mitotically active cells. These findings supported a diagnosis of plasmacytoma. This case emphasizes a diagnostic challenge in distinguishing round cell tumors in cats and the critical role of immunohistochemistry in achieving an accurate diagnosis. The tumor also showed aggressive clinical behavior, including suspected distant metastasis, and may have arisen in association with chronic inflammation at a prior injection site. Full article

The immunoglobulins (IG) or antibodies and the T cell receptors (TR) are the antigen receptors of the adaptive immune responses (AIR) of jawed vertebrates (Gnathostomata). IMGT^®, the international ImMunoGeneTics information system^®, was created in 1989 by Marie-Paule Lefranc (Laboratoire d’ImmunoGénétique Moléculaire (LIGM), Université de Montpellier and CNRS) to deal with and to manage the huge diversity of IG or antibodies and TR. The founding of IMGT^® marked the advent of immunoinformatics, a new science which emerged at the interface between immunogenetics and bioinformatics. For the first time, the IG and TR variable (V), diversity (D), joining (J) and constant (C) genes were officially recognized as ‘genes’, as were the conventional genes. The IMGT-ONTOLOGY CLASSIFICATION axiom and the concepts of classification have generated the IMGT nomenclature and the IMGT Scientific chart rules for assigning IMGT names to IG and TR genes and alleles of Homo sapiens and of any other jawed vertebrate species. The IMGT nomenclature is used for genes in locus, in sequences (genomic or rearranged, expressed or not) and in structures enabling comparative immunology, evolutionary immunogenetics, standardized analysis and comparison of IG and TR repertoires analysis in normal or pathologic situations. IMGT nomenclature is used in basic, veterinary, and medical research, in clinical applications (mutation analysis in leukemia and lymphoma), and in therapeutic antibody design, engineering and humanization. By providing consistent and high standard biocuration for the description of the IG and TR loci, genes and alleles, and for the analysis of the IG or antibody and TR-expressed rearranged sequences and proteins and structures, the IMGT nomenclature is the common language for immunoinformatics and artificial intelligence (AI). Full article

Background/Objectives: Duodenal lymphomas (DLs) are a rare subset of gastrointestinal lymphomas with incompletely characterized clinicopathological features due to low incidence and diagnostic challenges. This study assessed DL survival outcomes, characterized clinical/endoscopic features, and identified prognostic factors. Methods: This was a retrospective observational study of patients undergoing endoscopic examinations between 1 November 2002 and 1 November 2022 at Peking Union Medical College Hospital, with a subsequent histopathological diagnosis of DL. The primary outcome was overall survival (OS), and Cox proportional hazards modeling was used for survival analyses. Results: Sixteen patients (32%) had indolent B-cell lymphoma, 20 (40%) had aggressive B-cell lymphoma, and 14 (28%) had T-cell lymphoma. Diarrhea and weight loss were more common in patients with T-cell lymphoma. The most common endoscopic appearance was mucosal granularity, and 40% of patients had mass lesions. The median OS was 24.1 (95% CI: 13.3–117) months, with 1- and 5-year survival rates of 68.0% (95% CI: 56.2–82.2%) and 33.8% (95% CI: 22.3–51.44%), respectively. In multivariable analysis, a granular appearance (HR: 0.33, 95% CI: 0.11–0.99, and p = 0.049) and taking chemotherapy (HR: 0.22, 95% CI: 0.07–0.69, and p = 0.01) were associated with better OS, while T-cell lymphoma (HR: 9.19, 95% CI: 2.12–32.83, and p = 0.003) and stage IV lymphoma (HR: 12.76, 95% CI: 1.70–95.66, and p = 0.013) were associated with worse OS. Conclusions: This first integrated study provides new information on the clinical, endoscopic, and prognostic features of DL. While no specific clinical or endoscopic feature is diagnostic of DL, DL must remain in the differential diagnosis of any patient presenting with nonspecific gastrointestinal symptoms. Full article

Objective: Primary extranodal lymphomas of the head and neck region are relatively rare and represent a biologically distinct subset. The diagnosis and differential diagnosis of head and neck lymphomas are important and deserve special attention. The aim of the present study was to retrospectively evaluate patients diagnosed with primary head and neck lymphomas at the Department of Pathology between January 2020 and January 2026. Histopathological subtypes, localization, relative frequencies, and overall survival were analyzed. Materials and Methods: This retrospective study included 31 cases diagnosed with lymphoma involving the head and neck region. Medical records were reviewed. Histopathological slides were re-evaluated under light microscopy by experienced pathologists. All cases were classified according to the current World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues. An extensive immunohistochemical panel was applied. Statistical analysis was performed using SPSS statistical software (version 27.0; IBM Corp., Armonk, NY, USA). Results: The study group included 31 patients with head and neck lymphoma. The most common histological type was diffuse large B-cell lymphoma (DLBCL) (54.8%). Other histological subtypes included follicular lymphoma (FL), mantle cell lymphoma (MCL), extranodal NK/T-cell lymphoma (NKTCL), anaplastic large cell lymphoma (ALCL), and Hodgkin lymphoma (HL). The most common location was the tonsil (38.7%). Other locations included the nasopharynx, oral cavity, nasal cavity, salivary glands, and thyroid. Epstein–Barr virus (EBV) positivity was detected in two patients (6.5%), and human immunodeficiency virus (HIV) infection was identified in two patients (6.5%). At the time of the last follow-up, 27 patients (87.1%) were alive, whereas four patients (12.9%) had died. The mortality rate was 12.9%. The median overall survival was 28 months (95% CI: 10–45). Conclusions: Malignant lymphoma should be considered when evaluating head and neck masses, and histopathological assessment of the affected tissue remains the cornerstone of diagnosis. Full article

Cutaneous T-cell lymphoma (CTCL) comprises a heterogeneous group of extranodal non-Hodgkin lymphomas. With the publication of the fifth edition of the World Health Organization Classification of Hematolymphoid Tumors, the diagnostic framework for CTCL has shifted from primarily morphologic phenotypes toward an emphasis on molecular drivers. Current research suggests that malignant clones may arise from somatic mutations at the hematopoietic stem cell stage and may follow a continuous hematogenous dissemination model with bidirectional trafficking between the skin and systemic circulation. At the molecular level, genomic instability, often associated with somatic copy-number variations, may promote activation of the janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling pathway through gene-dosage effects. In parallel, chromatin remodeling linked to EZH2 overexpression and reduced special SATB1 expression may support a Th2-polarized program. This phenotype may contribute to epidermal barrier impairment via cytokines such as Interleukins-4 (IL-4) and IL-13, potentially creating conditions permissive for Staphylococcus aureus colonization. Microbial superantigens and exotoxins may further contribute to tumor progression and therapeutic resistance by reinforcing JAK/STAT signaling, particularly STAT3, and reducing CD8+ T-cell–mediated immune surveillance. In the dermis, reprogramming of cancer-associated fibroblasts and polarization of macrophages toward an M2 phenotype may collectively contribute to an immunosuppressive niche. Emerging biomarkers, including CD74, and acquired resistance mechanisms after anti-C-C chemokine receptor 4 therapy further extend the translational relevance of recent pathologic findings. Overall, CTCL evolution appears to be a systemic process shaped by interactions between tumor-intrinsic genetic alterations and the skin microenvironment. Full article

Plasma cell neoplasia is uncommon in cats, and multicentric nodal-predominant involvement has not been well characterized. This report describes a multicentric round cell neoplasia with plasmacytic differentiation in a 14-year-old Domestic Shorthair cat, emphasizing multimodal imaging features and treatment response. Contrast-enhanced computed tomography and magnetic resonance imaging were performed for staging and longitudinal assessment. Cytomorphology supported plasmacytic differentiation, and flow cytometry did not demonstrate an immunophenotype consistent with conventional B- or T-cell lymphoma. Because histopathology, immunohistochemistry, bone marrow evaluation, and assessment for monoclonal gammopathy were not performed, definitive classification was not possible; however, cytomorphology supported plasmacytic differentiation, with plasma cell neoplasia remaining an important diagnostic consideration. A hypofractionated radiotherapy protocol (36 Gy in six fractions) combined with systemic chemotherapy was administered. Serial imaging demonstrated complete radiologic resolution of the irradiated mass, whereas non-irradiated presumed nodal lesions progressed and an extradural spinal lesion subsequently developed. These findings highlight the capacity of round cell neoplasia with plasmacytic differentiation to mimic lymphoma on imaging and illustrate the dissociation between effective local control and ongoing systemic progression. Full article

Background and Objectives: Mycosis fungoides (MF) is the predominant subtype of cutaneous T-cell lymphoma, whereas large plaque parapsoriasis (LPP) closely resembles early-stage MF, making differential diagnosis challenging. Immune markers, such as CD47, CD163, and B7-H3, play crucial roles in tumor immune evasion and macrophage polarization. However, their expression profiles and potential diagnostic or prognostic implications in early-stage MF and LPP remain poorly defined. Therefore, this study aimed to evaluate the expression of CD47, CD163, and B7-H3 in early-stage MF and LPP and analyze their associations with clinicopathological characteristics and patient outcomes. Materials and Methods: This retrospective study evaluated the immunohistochemical expression of CD47, CD163, and B7-H3 in 46 patients with early-stage mycosis fungoides (MF) and 46 patients with large plaque parapsoriasis (LPP). Expression levels were assessed using an immunoreactivity scoring system and analyzed for their associations with clinical parameters and disease-free survival (DFS). The study included patients diagnosed and followed at Sivas Cumhuriyet University between 1 March 2015 and 31 March 2025. Results: High CD47 expression was detected in 72.7% of MF patients, high B7-H3 expression in 45.7%, and high CD163 expression in 46.7% compared with LPP patients (p < 0.001). These markers showed positive correlations, and elevated expression, especially of B7-H3 and CD163, was associated with shorter disease-free survival in univariate analysis. Conclusions: The higher expression of CD47, CD163, and B7-H3 in early-stage MF compared with LPP suggests that these markers may contribute to the differential diagnosis and could represent potential therapeutic targets; however, their independent prognostic value requires confirmation in larger studies. Full article

Background: Malignant lymphoma is the most common hematological malignancy; however, primary central nervous system lymphoma accounts for only a small percentage of non-Hodgkin lymphoma (NHL). Among these, primary cauda equina lymphoma (CEL) is extremely uncommon. Its rarity and atypical clinical presentation often make diagnosis challenging. Case Presentation: An 80-year-old man presented with progressive gait disturbance, lower-extremity weakness, and numbness. MRI revealed diffuse swelling and homogeneous gadolinium enhancement of the cauda equina at T12–L1; additionally, CSF cytology identified malignant lymphocytes. Open biopsy confirmed a diagnosis of diffuse large B-cell lymphoma. At diagnosis, the patient was classified as Ann Arbor stage IV, and the clinical parameters corresponded to a high-risk International Prognostic Index (IPI) category. The patient received five courses of immunochemotherapy with rituximab, methotrexate, vincristine, and procarbazine (R-MPV), resulting in marked radiological improvement and functional recovery, achieving a complete response. However, consolidation therapy was discontinued as the patient did not wish to continue. Unfortunately, intracranial relapse occurred four months later, and the patient ultimately succumbed to infectious complications. Only 29 cases of primary CEL have been reported. For all cases, a biopsy with histopathological examination is required for a definitive diagnosis. Currently, combined chemotherapy and radiotherapy are considered the standard treatment. This case was diagnosed through nerve biopsy with cauda equina at T12 to L1 levels, and immunochemotherapy successfully reduced the lesion while improving lower extremity function. Conclusions: Despite the considerable burden on patients, nerve biopsy is necessary for primary CEL to obtain a diagnosis and an early therapeutic approach for both neurological and vital prognoses. Full article

Background: Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) exhibit substantial heterogeneity, reflecting the diversity of the germinal center (GC). Histologic transformation of FL to DLBCL is associated with poor prognosis, yet robust biomarkers predicting transformation remain limited. Methods: We integrated single-cell DNA sequencing, single-cell RNA sequencing, and spatial transcriptomics in diagnostic lymph-node biopsies from non-transformed FL (ntFL), transformed FL (tFL), and DLBCL to characterize clonal states and immune niches in GC lymphomas. T-cell signatures associated with transformation were evaluated in an independently published single-cell FL dataset. Results: Transcriptional profiling revealed similarities between tFL and DLBCL, consistent with a GC-related malignant program. The tFL microenvironment showed enrichment of exhausted CD4⁺ regulatory and CD8⁺ effector T cells, together with CD4⁺ follicular helper T cells (Tfh) displaying an adhesion-related phenotype. Spatial analysis suggested increased proximity of exhausted/immunosuppressive T cells and enhanced Tfh-B-cell interactions in tFL compared with ntFL. These immune signatures were also observed in an external cohort and were associated with early transformation. In addition, clonal hematopoiesis-associated mutations were detected in microenvironmental cells across samples, suggesting a potential contribution to the lymphoma microenvironment. Conclusions: This work demonstrates the feasibility of integrating single-cell and spatial analyses in GC lymphomas and provides a framework for investigating tumor heterogeneity and immune organization. These findings may inform future studies on biomarker development and the rational design of immunotherapies. Full article

Chimeric antigen receptor T (CAR-T) cell therapy has become a standard of care for many hematological malignancies, and has significantly transformed treatment outcomes. However, CAR-T therapy is associated with specific toxicities, including infections. Although the anti-CD19 CAR-T risks are well-characterized, infectious complications following B-cell maturation antigen (BCMA)-directed CAR-T in multiple myeloma (MM) remain under-researched. In this study, we evaluated the incidence and clinical impact of cytomegalovirus (CMV), Epstein–Barr virus (EBV), and adenovirus (ADV) reactivations in 75 patients receiving anti-BCMA CAR-T for MM, and compared them to 60 patients receiving commercial anti-CD19 CAR-T for B-cell lymphoma (BCL). The viral reactivation rates were 20% for CMV and 8% for EBV in the MM group, vs. 31.7% and 3%, respectively, in the BCL group. No ADV reactivations were seen in either cohort. Most of the CMV reactivations (87% in the MM cohort and 68.5% in the BCL cohort) were asymptomatic and clinically insignificant, and had no impact on progression-free survival (PFS) or overall mortality. Overall, these findings suggest that although CMV and EBV reactivations are relatively common after anti-BCMA CAR-T, they are rarely associated with meaningful disease, and the risks do not exceed those of CD19-directed therapy. Thus, routine pre-emptive screening for these viruses may be unwarranted in asymptomatic patients. Full article

Background/Objectives: T-cell lymphomas are relatively common in veterinary species, yet current diagnostic tools such as PCR-based clonality assays often lack sensitivity and specificity. In humans, we recently developed two related tissue-based diagnostic approaches based on the differential detection of the mutually exclusively expressed TCRbeta1 and 2 (TCRβ1 and 2) constant region proteins, or the corresponding TRBC1 and TRBC2 transcripts. Analogous to the detection of kappa/lambda light chains for the diagnosis of B-cell/plasma cell neoplasms in human clinical practice, our TCRβ1/2 diagnostic assay has the potential to transform veterinary diagnostic workflows. Methods: We identified and confirmed the sequences of the relevant TRBC1 and TRBC2 sequences in both cats and dogs, focusing on the 3′ untranslated region (UTR), where there is the least sequence homology between TRBC1 and TRBC2. To allow us to design appropriate probe sequences, we confirmed a lack of 3′UTR in either species, and we observed limited 3′ untranslated region UTR sequence polymorphism in the cat but not in the dog 3′UTR. We designed BaseScope™ RNA in situ hybridization probes targeting the 3′ UTR to distinguish between TRBC1 and TRBC2 transcripts in formalin-fixed paraffin-embedded tissues. Results: In normal tissues, we found the TRBC2:TRBC1 expression ratio to be similar to the 1.2:1 ratio in humans, between 1:1 and 3:1, skewing towards TRBC2, in both dogs and cats. These findings were corroborated using quantitative reverse transcription PCR. Applying our in situ hybridization probes to cases of T-cell lymphoma in dogs and cats, we demonstrated that an assay for differential expression of TRBC1 and TRBC2 in T-cell populations could identify clonal T-cell populations, as in human diagnostics. If further studies corroborate this proof-of-concept study, TRBC1/2 detection could obviate the need for slow, complex and expensive multiplexed PCR-based (PCR for antigen receptor rearrangements (PARR)) clonality assays. Conclusions: This study provides proof-of-concept data for a novel diagnostic approach that could simplify and substantially improve the accuracy of lymphoma diagnostics in veterinary medicine, by detecting TRBC1/2 transcripts. Full article

Mycosis fungoides (MF) is a rare primary cutaneous T-cell lymphoma (pCTCL) that generally has an indolent course with a favorable prognosis. However, numerous clinical variants have been described that differ substantially from classic Alibert–Bazin MF, resulting in altered prognosis, treatment response, and patient outcomes. This narrative review considers rare MF variants—bullous, ichthyosiform, hypopigmented, folliculotropic, poikilodermatous, granulomatous, granulomatous slack skin, pagetoid reticulosis and syringotropic MF—with emphasis on practical diagnostic approaches for clinicians. Given that MF can mimic more than 50 different dermatoses and is frequently associated with prolonged diagnostic delay, we provided detailed clinical and dermoscopic features that should raise diagnostic suspicion and guide biopsy decisions. We discussed extensive differential diagnoses for each variant and highlighted MF’s status as dermatology’s “great imitator.” Additionally, we addressed the risk of second primary malignancy in patients with MF, as well as the genetic and microenvironmental factors proposed to contribute to its clinical heterogeneity. Furthermore, we evaluated existing classification systems and suggested future directions that integrate molecular data and tumor biology to improve prognostic assessment and guide therapeutic decision-making. Full article

Background: X-linked immunodeficiency with magnesium defect, Epstein–Barr virus (EBV) infection, and neoplasia (XMEN) disease is a rare inborn error of immunity caused by loss-of-function mutations in MAGT1, leading to impaired N-linked glycosylation. Although chronic EBV viremia is a hallmark of XMEN disease, the mechanisms underlying its marked clinical heterogeneity remain poorly understood. Methods: We performed an in-depth clinical, immunological, and genetic characterization of two siblings carrying a pathogenic MAGT1 variant (c.369_370insCC; p.Gly124fs), validated and deposited in ClinVar (SCV007293792). Assessments included whole-exome sequencing, multiparametric flow cytometry focusing on NKG2D expression, and longitudinal clinical follow-up. Results: Despite shared absence of NKG2D expression, the siblings exhibited strikingly divergent phenotypes. One sibling developed progressive neurodegeneration with central nervous system atrophy. The other presented with a complex immuno-hematologic phenotype, including EBV-positive Hodgkin lymphoma, recurrent autoimmune cytopenias, and lymphoma-associated thrombotic microangiopathy, representing a novel clinical association in XMEN disease. Comparative immunophenotyping revealed shared defects in B-cell maturation but distinct T-cell differentiation patterns. To contextualize neurological variability, we propose a descriptive, hypothesis-generating three-category conceptual classification comprising early-onset neurodevelopmental forms, adult-onset neurodegenerative manifestations, and secondary immune-mediated or vascular involvement of the nervous system. Conclusions: These findings demonstrate profound intrafamilial heterogeneity in XMEN disease and suggest a model in which modifier-sensitive factors influence organ-specific disease expression. The observation of lymphoma-associated thrombotic microangiopathy and the proposed descriptive neurological classification provide a conceptual framework that may help guide tailored, multidisciplinary surveillance beyond the primary genetic defect. Full article

T-cell non-Hodgkin lymphomas, which arise from post-thymic mature T cells, constitute approximately 10–15% of all non-Hodgkin lymphomas. Their leukemic presentations, referred to here as mature T-cell leukemias, are relatively uncommon and present significant diagnostic and therapeutic challenges requiring an informed approach to diagnosis and management. The initial presentation is often persistent T-cell lymphocytosis that must be distinguished from reactive (non-malignant) causes. Unlike B-cell lymphocytosis, where clonality usually indicates malignancy, T-cell clonality can be detected in benign conditions such as autoimmune disorders and viral infections. Thus, establishing clonality is helpful but not sufficient, and a systematic diagnostic approach integrating clinical features, morphology, immunophenotype, and molecular findings is critical. This review outlines our approach to the diagnosis and treatment of four major subtypes of mature T-cell leukemias: T-cell prolymphocytic leukemia (T-PLL), adult T-cell leukemia/lymphoma (ATLL), T-large granular lymphocytic leukemia (T-LGL), and Sézary syndrome (SS). Each section includes a discussion of clinical features, workup, and treatment options. Full article

Background: Glofitamab is a bispecific antibody engaging CD3 on T-cells and CD20 on B-cells. Glofitamab is approved for the treatment of relapsed, refractory diffuse large B-cell lymphoma (R/R DLBCL). Lymphocyte-activation gene 3 (LAG3) and T-lymphocyte-associated protein 4 (CTLA4) are immune checkpoint receptors with inhibitory effects on T-cell activity. There are several common germline variants of both receptor genes. Methods: Here, we evaluate clinical outcomes in R/R DLBCL patients treated with glofitamab according to the single-nucleotide polymorphisms LAG3 rs870849 and CTLA4 rs231775. Results: While there was no apparent association of CTLA4 genotype with glofitamab treatment outcomes, significant differences emerged in LAG3 rs870849 carriers with extended progression-free and overall survival in homozygous LAG3 T455, intermediate PFS and OS in heterozygous LAG3 I455T, and short PFS and OS in homozygous LAG3 I455 carriers. Conclusions: LAG3 rs870849 may be a prognostic response marker in R/R DLBCL treated with glofitamab. Full article